Purohit, P. K., Edwards, R., Tokatlidis, K. and Saini, N. (2019) MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells. RNA Biology, 16(7), pp. 918-929. (doi: 10.1080/15476286.2019.1600999) (PMID:30932749) (PMCID:PMC6546347)
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Abstract
Mitochondrial dynamics is a highly dysregulated process in cancer. Apoptosis and mitochondrial fission are two concurrent events wherein increased mitochondrial fragmentation serves as a hallmark of apoptosis. We have shown earlier that miR-195 exerts pro-apoptotic effects in breast cancer cells. Herein, we have demonstrated miR-195 as a modulator of mitochondrial dynamics and function. Imaging experiments upon miR-195 treatment have shown that mitochondria undergo extensive fission. We validated mitofusin2 as a potential target of miR-195. Which may provide a molecular explanation for the respiratory defects induced by miR-195 over-expression in breast cancer cells? Active, but not total, mitochondrial mass, was reduced with increasing levels of miR-195. We have further shown that miR-195 enhances mitochondrial SOD-2 expression but does not affect PINK1 levels in breast cancer cells. Collectively, we have revealed that miR-195 is a modulator of mitochondrial dynamics by targeting MFN2 thereby impairing mitochondrial function. Concomitantly, it enhances the scavenger of reactive oxygen species (SOD-2) to maintain moderate levels of oxidative stress. Our findings suggest a therapeutic potential of miR-195 in both ER-positive as well as ER-negative breast cancer cells.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the Council of Scientific and Industrial Research, India [BSC0123];Newton Fund [269852058];Scottish Office Home and Health Department (GB) [WM120111];Biotechnology and Biological Sciences Research Council (GB) [BB/R009031/1)];Scottish Office Home and Health Department [HR07019)]. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tokatlidis, Professor Kostas and Edwards, Mr Ruairidh |
| Authors: | Purohit, P. K., Edwards, R., Tokatlidis, K., and Saini, N. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Life Sciences |
| Journal Name: | RNA Biology |
| Publisher: | Taylor & Francis |
| ISSN: | 1547-6286 |
| ISSN (Online): | 1555-8584 |
| Published Online: | 01 April 2019 |
| Copyright Holders: | Copyright © 2019 Informa UK Limited, trading as Taylor and Francis Group |
| First Published: | First published in RNA Biology 16(7):918-929 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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